Nitrogen → N4-Isopropyl-N2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidine-2,4-diamine

HRID 59138Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:7]=[CH:8][C:9]=1[N:10]1[CH:14]=[C:13]([CH3:15])[N:12]=[CH:11]1)[NH2:6].Cl[C:17]1[N:22]=[C:21]([NH:23][CH:24]([CH3:26])[CH3:25])[CH:20]=[C:19]([CH2:27][O:28][CH2:29][C:30]([F:33])([F:32])[F:31])[N:18]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.N#N>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:24]([NH:23][C:21]1[CH:20]=[C:19]([CH2:27][O:28][CH2:29][C:30]([F:32])([F:33])[F:31])[N:18]=[C:17]([NH:6][C:5]2[CH:7]=[CH:8][C:9]([N:10]3[CH:14]=[C:13]([CH3:15])[N:12]=[CH:11]3)=[C:3]([O:2][CH3:1])[CH:4]=2)[N:22]=1)([CH3:26])[CH3:25]

Participants

Conditions

Temperature: 120 °C

Procedure

3-Methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline (90 mg, 0.44 mmol), 2-chloro-N-isopropyl-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-4-amine (63 mg, 0.22 mmol), cesium carbonate (145 mg, 0.44 mmol), palladium acetate (7.48 mg, 0.03 mmol) and 2-(dicyclohexylphosphino)-biphenyl (11.68 mg, 0.03 mmol) in dioxane (1.5 mL) were mixed in a vial under N2 atmosphere. The mixture was heated at 120° C. in a microwave reactor for 90 minutes. The mixture was filtered through diatomeous earth and the filter plug was washed with methanol. The solvents were evaporated and the residue was purified by preparative HPLC to give the title compound as a solid 60 mg (60%).

Workup

filtrationThe mixture was filtered through diatomeous earth
washthe filter plug was washed with methanol
customThe solvents were evaporated
customthe residue was purified by preparative HPLC

Sources & evidence

ORD record: ord-a1622811e49b4642bf9da8d75fff171f
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09439904B2

Reaction notes

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